Previous studies have demonstrated that growth of breast cancer may be dependent on a variety of sterood and peptide hormones. Recently, it has been shown that growth of a variety of normal and malignant tissues may be controlled by one or more of several newly characterized polypeptide growth factors present in serum. The objective of this proposal is to examine the mitogenic and/or regulatory roles of several of these newly recognized polypeptide growth factors on human breast cancer. These polypeptides include the somatomedins, epidermal growth factor, and pituitary fibroblast growth factor. Each polypeptide will be examined for its ability to bind to specific cellular receptors and subsequently alter macromolecular synthesis, growth, and other metabolic events in several human breast cancer cell lines maintained in long-term tissue culture. In addition, potential interactions between these peptides, steroid hormones and insulin will also be studied at the biochemical level. Finally, the somatomedin polypeptides will also be studied in rats with carcinogen-induced mammary tumors to evaluate their physiologic significance in vivo.